WO2017188157A1 - Agent pour réguler le rapport de composition de la flore bactérienne intestinale, médicament, aliment, boisson et procédé de régulation du rapport de composition de la flore bactérienne intestinale - Google Patents

Agent pour réguler le rapport de composition de la flore bactérienne intestinale, médicament, aliment, boisson et procédé de régulation du rapport de composition de la flore bactérienne intestinale Download PDF

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WO2017188157A1
WO2017188157A1 PCT/JP2017/016071 JP2017016071W WO2017188157A1 WO 2017188157 A1 WO2017188157 A1 WO 2017188157A1 JP 2017016071 W JP2017016071 W JP 2017016071W WO 2017188157 A1 WO2017188157 A1 WO 2017188157A1
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culture
composition ratio
intestinal
negative
clostridium
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PCT/JP2017/016071
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English (en)
Japanese (ja)
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順博 戸田
康博 日高
源一郎 杣
孝志 西澤
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ティーエフケイ株式会社
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Priority to EP17789440.9A priority Critical patent/EP3449932A4/fr
Priority to US16/095,878 priority patent/US20190125805A1/en
Priority to JP2018514568A priority patent/JPWO2017188157A1/ja
Priority to KR1020187030171A priority patent/KR20180137494A/ko
Priority to CN201780025931.9A priority patent/CN109152802A/zh
Publication of WO2017188157A1 publication Critical patent/WO2017188157A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells

Definitions

  • the present invention relates to an intestinal flora constituent ratio adjusting agent, pharmaceuticals, foods and drinks, and a method for adjusting the intestinal flora constituent ratio.
  • Patent Literature 1 proposes a weight gain inhibitor, a neutral fat reducing agent, and a slimming agent that adjust the intestinal flora constituent ratio with an extract of a Salacia plant (Patent Literature 1).
  • an object of the present invention is to provide a new safe intestinal flora constituent ratio adjusting agent and a method for adjusting the intestinal flora constituent ratio.
  • the intestinal flora constituent ratio adjusting agent of the present invention is an intestinal flora constituent ratio adjusting agent that adjusts the constituent ratio of the intestinal microflora, It is characterized in that it contains at least one of Rhodobacter azotoforms BP0899 strain (Accession No. NITE BP-644) and its culture.
  • the method for adjusting the gut microbiota composition ratio of the present invention is a method for adjusting the gut microbiota composition ratio, It comprises a step of administering an intestinal flora constituent ratio adjusting agent comprising at least one of Rhodobacter azotoformans BP0899 strain (Accession No. NITE BP-644) and its culture.
  • Rhodobacter azotoformans (Accession No. NITE BP-644) BP0899 and its culture.
  • the intestinal flora constituent ratio was found to be adjustable, and the present invention was achieved.
  • At least one of Rhodobacter azo preparative folder performance (Rhodobacter azotoformans) BP0899 strain (Accession No. NITE BP-644) and the culture is highly safe and can be administered over a long period.
  • 1, in the embodiment, is a graph showing changes in Bacteroides (Bacteroides) genus composition ratio in the gut flora of mice.
  • 2, in the embodiment, is a graph showing a change in composition ratio of Lactobacillus (Lactobacillus) genus in the intestinal flora of mice.
  • 3, in the embodiment is a graph showing changes in Prevotella (Prevotella) genus composition ratio in the gut flora of mice.
  • 4, in the embodiment is a graph showing a change in composition ratio of Clostridium cluster XVIII (Clostridium claster XVIII) in the gut flora of mice.
  • 5 is a graph showing changes in the composition ratio of Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) in the intestinal flora of mice in Examples.
  • 6, in the embodiment is a graph showing a change in composition ratio of Clostridium cluster XI (Clostridium claster XI) in the gut flora of mice.
  • 7, in the embodiment is a graph showing changes in Bacteroides (Bacteroides) genus composition ratio in the gut flora of mice.
  • 8, in the embodiment is a graph showing a change in composition ratio of Lactobacillus (Lactobacillus) genus in the intestinal flora of mice.
  • FIG. 9 is a graph showing changes in Prevotella (Prevotella) genus composition ratio in the gut flora of mice.
  • 10 in the embodiment, is a graph showing a change in composition ratio of Clostridium cluster XVIII (Clostridium claster XVIII) in the gut flora of mice.
  • FIG. 11 is a graph showing changes in the composition ratio of Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) in the intestinal flora of mice in Examples.
  • 12, in the embodiment is a graph showing a change in composition ratio of Clostridium cluster XI (Clostridium claster XI) in the gut flora of mice.
  • Rhodobacter azotoformans BP0899 strain (Accession No. NITE BP-644) and its culture are the following (1) to (30): It is preferable to have mycological characteristics of The BP0899 strain was deposited under the accession number NITE P-644 at the Patent Organism Depositary Center of the National Institute of Technology and Evaluation (2-5-8 Kazusa-Kamashita, Kisarazu City, Chiba, Japan) (Accession date: 2008) In addition, the deposit was made internationally under the deposit number NITE BP-644 (transfer date: October 27, 2010).
  • the base sequence of 16S rRNA of the BP0899 strain is preferably the base sequence represented by SEQ ID NO: 1.
  • Bacteroides Bacteroides (Bacteroides) genus Lactobacillus (Lactobacillus) genus Prevotella (Prevotella) genus Clostridium cluster XVIII (Clostridium claster XVIII), Clostridium subcluster XIVa (Clostridium subclaster XIVa) and increase the component ratio of the at least one enteric bacteria selected from the group consisting of Clostridium cluster XI (Clostridium claster XI), or, it is preferable to suppress the reduction in component ratio.
  • the pharmaceutical product of the present invention is a pharmaceutical product for adjusting the intestinal flora constituent ratio, and includes the intestinal flora constituent ratio adjusting agent of the present invention.
  • the food / beverage product of the present invention is a food / beverage product having a function of adjusting the gut microbiota composition ratio, and includes the gut microbiota composition ratio regulator of the present invention.
  • the intestinal flora constituent ratio adjusting agent of the present invention is an intestinal flora constituent ratio adjusting agent that adjusts the constituent ratio of the intestinal flora, and is at least one of the BP0899 strain and its culture. It is characterized by including.
  • the intestinal flora constituent ratio adjusting agent of the present invention contains at least one of a red non-sulfur bacterium and a culture of the red non-sulfur bacterium, and the red non-sulfur bacterium is Rhodobacter azotoformans.
  • the Rhodobacter azotoformans may include the Rhodobacter azotoforms BP0899 strain (Accession Number NITE BP-644).
  • At least one of the BP0899 strain which is the red non-sulfur bacterium and the culture thereof have the following mycological characteristics (1) to (30).
  • At least one of the BP0899 strain which is the red non-sulfur bacterium, and its culture may further exhibit the properties shown in the following table (31), for example, under aerobic culture conditions in a dark place.
  • Table (31) for example, under aerobic culture conditions in a dark place.
  • “ ⁇ ” indicates no production
  • “+” indicates production.
  • the mycological characteristics may be evaluated, for example, from the result of further main culture after pre-culture.
  • the preculture may be performed, for example, by inoculating the BP0899 strain, which is the red non-sulfur bacterium, on a normal agar medium and culturing at 30 ° C. for 24 hours.
  • the conditions of the main culture can be appropriately set according to the evaluation method of each mycological feature.
  • the culture conditions of (1) to (5) are, for example, aerobic culture in a dark place at 30 ° C. using a normal agar medium, and the culture conditions of (6) to (7) Is, for example, an anaerobic culture at 30 ° C.
  • the culture conditions of (8) to (12) are, for example, each medium, preferably at 30 ° C. in a dark place.
  • (13), (14), (16), (17), (19) to (23), (25) oxidation test, (26), (29), (30) and (30) 31) is an aerobic culture in the dark, for example, the fermentation test of (15), (18), (24), (25), and (27) and (28) are, for example, in the dark Anaerobic culture.
  • the method for testing these mycological characteristics is not particularly limited, and a conventionally known method can be employed. Specifically, for example, Barrow G. et al. I. And Feltham R .; K. A.
  • Denitrification reaction is positive if growth and gas formation are observed under anaerobic culture conditions using 1% sodium nitrate broth.
  • a gas generation and a dark blue color determined under anaerobic culture conditions using the above-mentioned Giltay medium (pH 7.0 to 7.2) containing a Durham tube is positive as a denitrification reaction. To do.
  • the above-mentioned Giltay medium is composed of solution A (1 g of KNO 3, 1 g of asparagine, 5 mL of 1% bromothymol blue alcohol solution and 500 mL of distilled water) and solution B (8.5 g of sodium citrate, 1 g of MgSO 4 ⁇ 7H 2 O, FeCl 3 ⁇ 6H 2 O 0.05 g, KH 2 PO 4 1 g, CaCl 2 ⁇ 6H 2 O 0.2 g and distilled water 500 mL).
  • a commercially available bacteria identification kit for the said test method, for example. Although it does not restrict
  • At least one of the BP0899 strain, which is the red non-sulfur bacterium, and its culture may further have the following mycological characteristics (32) to (40).
  • the method for testing the mycological characteristics of (32) to (40) is not particularly limited, and a conventionally known method can be adopted. Specifically, for example, the methods described in the above-mentioned documents and the like can be mentioned. Moreover, you may use a commercially available bacteria identification kit for the said test method, for example. Although it does not restrict
  • the intestinal flora constituent ratio adjusting agent of the present invention may further contain other red non-sulfur bacteria other than at least one of the BP0899 strain and its culture.
  • the other purple non-sulfur bacteria is not particularly limited, for example, Rodosupirurimu (Rhodospirillum) genus Rodoshisuta (Rhodocista) genus Rodopira (Rhodopila) genus Rodomikurobiumu (Rhodomicrobium) genus, blasting black squirrel (Blastochloris) genus Rodopuranesu (Rhodoplanes ) genus Rodobiumu (Rhodobium) genus Rodoshikurusu (Rhodocyclus) genus Rodoferakusu (Rhodoferax) genus include Rhodopseudomonas (Rhodopseudomonas) genus bacteria such.
  • the other red non-sulfur bacteria include, for example, Rhodobacter azotoformans BP0899 strain (Accession No. NITE BP-644) and at least one of its cultures, Rhodobacter azotoformans ( Rhodobacter azotoformans), it may be the Rhodobacter azo preparative folder performance (Rhodobacter azotoformans) other than Rhodobacter (Rhodobacter) genus of bacteria.
  • red non-sulfur bacteria including the BP0899 strain
  • soil seawater, river water, lake water, swamp water, etc. Is mentioned.
  • soil include, but are not limited to, land, sea bottom, river bottom, lake bottom and marsh bottom soil, sand, and mud.
  • a method for isolating the red non-sulfur bacteria for example, a conventionally known collection method, culture method or the like can be used, and there is no particular limitation.
  • the isolation method for example, when the collection source is lake water, the collected lake water is filtered through a filter or the like, the filtrate is cultured on an agar medium or the like, and the red non-sulfur bacteria are isolated from the obtained colonies. May be.
  • the collection source is mud
  • the collected mud is suspended in a buffer solution, etc., and then the suspension is centrifuged, and the obtained supernatant is cultured on an agar medium or the like.
  • the red non-sulfur bacterium may be isolated.
  • the isolated red non-sulfur bacterium may be further cultured, for example, in a liquid medium.
  • the intestinal flora constituent ratio adjusting agent of the present invention may further contain other bacteria in addition to the red non-sulfur bacteria.
  • the other bacteria are not particularly limited, and examples thereof include lactic acid bacteria and yeasts, and preferably lactic acid bacteria.
  • lactic acid bacteria is not particularly limited, for example, Lactobacillus acidophilus (Lactobacillus acidphilus), Lactobacillus casei (Lactobacillus casei), Lactobacillus lactis (Lactobacillus lactis), Lactobacillus bulgaricus (Lactobacillus bulgaricus), Lactobacillus Bacillus helveticus (Lactobacillus helveticus), Lactobacillus Deruburyukki (Lactobacillus delbrueckii), Lactobacillus plantarum (Lactobacillus plantarum), Lactobacillus brevis (Lactobacillus brevi ), Lactococcus lactis (Lactococcus lactis), Bifidobacterium longum (Bifidobacterium longum), Bifidobacterium breve (Bifidobacterium breve), Enterococcus faecalis (Ent
  • Saccharomyces cerevisiae Saccharomyces cerevisiae
  • Saccharomyces carlsbergensis Saccharomyces carlsbergensis
  • Saccharomyces ellipsometry Lee Deus Saccharomyces ellipsoideus
  • Saccharomyces Roukishi Saccharomyces rouxii
  • the medium is not particularly limited.
  • a medium containing a lower fatty acid, a medium added with malic acid, a culture medium 802 “DAIGO” (manufactured by Nippon Pharmaceutical Co., Ltd.) (Hiraishi and Kitagawa, Bulletin of the Japan Society of Scientific Fisheries, 1984, 50, 11, p. 1929-1937), modified MYS medium, growth medium and the like preferably, a medium containing lower fatty acids, Malic acid-added medium, L-dried culture medium 802 “DAIGO” (manufactured by Nippon Pharmaceutical Co., Ltd.).
  • Examples of the lower fatty acid-added medium and malic acid-added medium include a medium obtained by adding biotin, vitamin B 1 , nicotinic acid, a lower fatty acid, or a sodium salt of malic acid to the basal medium shown in Table 1 below. Although it does not restrict
  • modified MYS medium and the growth medium include media having the compositions shown in Tables 2 and 3 below.
  • the temperature range is not particularly limited, but is, for example, 23 to 39 ° C. or 30 ° C.
  • the pH range is not particularly limited, but is, for example, pH 5.5 to 8.5, 6.0 to 8.5, or 7.0.
  • the culture may be performed, for example, under an aerobic condition or an anaerobic condition, and is not particularly limited, but is preferably an anaerobic condition.
  • the light conditions during the culture are not particularly limited, and may be, for example, dark conditions or illumination conditions, but preferably under an illuminance of 2000 lux to 10000 lux.
  • the culture may be performed, for example, in a sealed illumination type culture tank. Moreover, you may culture
  • the culture time is not particularly limited, and may be, for example, until the growth of the red non-sulfur bacteria reaches a stationary phase.
  • the culture time may be, for example, 72 hours.
  • red non-sulfur bacterium for example, only the red non-sulfur bacterium may be cultured, or other bacteria may be mixed and cultured at the same time. Although it does not restrict
  • the 16S rRNA base sequence of the BP0899 strain is preferably the base sequence represented by SEQ ID NO: 1.
  • the base sequence of the 16S rRNA can be determined, for example, by extracting DNA from the BP0899 strain isolated and cultured by the method described above and using a primer or the like.
  • the method for extracting the DNA and determining the base sequence can be, for example, a conventional method and is not particularly limited.
  • the primer is not particularly limited, and examples thereof include the following primers.
  • the culture of the red non-sulfur bacterium examples include, but are not particularly limited to, the cell body of the red non-sulfur bacterium, the culture supernatant of the red non-sulfur bacterium, and the cell extract of the red non-sulfur bacterium. .
  • the intestinal flora constituent ratio adjusting agent of the present invention may further contain a culture of bacteria other than the red non-sulfur bacteria.
  • the culture of bacteria other than the red non-sulfur bacteria is not particularly limited, and examples thereof include cells of other bacteria described above, culture supernatants of the other bacteria, cell extracts of the other bacteria, and the like. Can be mentioned.
  • Specific examples of the culture of bacteria other than the red non-sulfur bacterium include, for example, the aforementioned lactic acid bacteria, dry cells such as yeast, extracts and the like.
  • the culture may be, for example, a processed product of the bacterial cell, a processed product of the culture supernatant, a processed product of the bacterial cell extract, or the like, and is not particularly limited.
  • the treated product is not particularly limited.
  • the culture concentrate dried product, lyophilized product, solvent-treated product, surfactant-treated product, enzyme-treated product, protein fraction product, and sonicated product. , Milled products and the like.
  • the culture is, for example, a mixture of the cells, the culture supernatant, the cell extract, the processed product of the cell, the processed product of the culture supernatant, the processed product of the cell extract, etc. But you can.
  • the mixture can be mixed in any combination and ratio, and is not particularly limited.
  • the combination is not particularly limited, and examples thereof include a mixture of the cells and the culture supernatant.
  • the intestinal flora constituent ratio adjusting agent of the present invention may further contain other components such as additives.
  • the additive is not particularly limited, and examples thereof include a stabilizer.
  • the method for producing the intestinal flora constituent ratio adjusting agent is not particularly limited, and for example, a commonly used formulation technique can be adopted.
  • the intestinal bacterial flora composition ratio modifier of the present invention for example, Bacteroides (Bacteroides) genus Lactobacillus (Lactobacillus) genus Prevotella (Prevotella) genus Clostridium cluster XVIII (Clostridium claster XVIII), to increase the clostridial subcluster XIVa (Clostridium subclaster XIVa) and Clostridium cluster XI (Clostridium claster XI) component ratio enterobacteria such, or, it is possible to suppress the reduction in the component ratio .
  • Bacteroides Bacteroides
  • Lactobacillus Lactobacillus
  • Prevotella Prevotella
  • Clostridium cluster XVIII Clostridium claster XVIII
  • Clostridium cluster XI Clostridium claster XI
  • Clostridium subcluster XIVa Clostridium subcluster XIVa
  • the peroxisome proliferator-activated receptor ⁇ (Peroxisome Proliferator-Activated Receptor ⁇ ) activation improves cardiovascular and vascular diseases such as antivascular failure, lipid metabolism abnormality and arteriosclerosis, gastrointestinal diseases, renal diseases, malignant tumors and Alzheimer's disease, and immune regulation It has also been reported to have an effect.
  • the intestinal bacterial flora composition ratio regulator of the present invention for example, the composition ratio of intestinal bacteria producing such short-chain fatty acids such as butyric acid can be increased.
  • the composition ratio of Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) that produces short-chain fatty acids such as butyric acid can be increased by administration of the intestinal flora constituent ratio regulator of the present invention. Therefore, the gut microbiota composition ratio adjusting agent of the present invention is, for example, diabetes, obesity, cardiovascular diseases such as antivascular failure or lipid metabolism abnormality / arteriosclerosis, digestive diseases, renal diseases, malignant tumors and Alzheimer's disease can be improved and has an immunomodulatory action. Further, according to Patent Document 1, at the time of obese humans, the component ratio of Bacteroides (Bacteroides) genus in the intestine has been reported to decrease.
  • Bacteroides Bacteroides
  • composition ratio modifier of the present invention by increasing the composition ratio of Bacteroides (Bacteroides) genus, for example, believed to be improved obesity.
  • composition ratio of Prevotella ( Prevotella ) genus and Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) in the intestine decreases in patients with multiple sclerosis (Miyake S. et al. al (2015), PLOS One, 10. e0137429).
  • composition ratio of at least one of the Prevotella ( Prevotella ) genus and Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) by the administration of the intestinal microbiota composition ratio adjusting agent of the present invention, for example, multiple sclerosis Can be improved. Furthermore, according to Filip et al., It is reported that the composition ratio of the Prevotella genus in Parkinson's disease patients decreases (Filip S. et al (2015), Movement Disorders, Vol. 30, No.3, p.350-358).
  • Parkinson's disease can be improved by increasing the constituent ratio of the genus Prevotella ( Prevotella ) by administering the intestinal flora constituent ratio adjusting agent of the present invention.
  • the genus Lactobacillus is also widely known as a good fungus.
  • administration of the intestinal flora composition ratio modifier of the present invention by increasing the composition ratio of Lactobacillus (Lactobacillus) genus, for example, believed to be improved constipation.
  • the pharmaceutical product of the present invention is a pharmaceutical product for adjusting the intestinal microflora constituent ratio, and is not limited except that it contains the intestinal microbiota constituent ratio adjusting agent of the present invention.
  • pharmaceutical products include pharmaceutical products and quasi drugs.
  • Examples of the pharmaceutical dosage form include powders, fine granules, granules, tablets, coated tablets, capsules, troches, liquids and the like, and are not particularly limited.
  • the composition of the pharmaceutical is not particularly limited, and includes, for example, various additives such as excipients, binders, lubricants, disintegrants, absorption promoters, emulsifiers, stabilizers, preservatives, and the like. May be.
  • the said pharmaceutical can be manufactured with the formulation technique etc. which are used normally.
  • the animal species to which the pharmaceutical is administered is not particularly limited, and examples thereof include humans, non-human mammals such as monkeys, cows, pigs, dogs, and cats, birds such as chickens, and seafood.
  • the administration method is not particularly limited, and examples thereof include oral administration and parenteral administration.
  • Examples of the parenteral administration include transdermal absorption, injection, and suppository administration.
  • the dosage of the pharmaceutical agent can be appropriately set according to, for example, animal species, age, etc., and is not particularly limited.
  • the administration method, the administration subject, and the like are the same, for example.
  • the food / beverage products of this invention are food / beverage products which have the adjustment function of an intestinal microflora composition ratio, Comprising: It does not restrict
  • the food and drink includes general foods and health functional foods. Although it does not specifically limit as said general food, For example, grain processed food, vegetable processed food, fruit processed food, meat processed food, marine products processed food, dairy product, drink, health food etc. are mentioned.
  • the food / beverage products of this invention may contain the said intestinal microflora constituent ratio regulator as a raw material, an additive, etc., for example.
  • the processed grain food is not particularly limited, and examples thereof include wheat flour, rice flour, cereal bar, rice cracker, hail, and cookies. Although it does not restrict
  • the fruit processed food is not particularly limited, and examples thereof include fruit puree and dried fruit.
  • the meat processed food is not particularly limited, and examples thereof include ham, bacon, sausage and the like. Although it does not restrict
  • the health functional food is also generally referred to as functional food.
  • the health functional foods include foods for specified health use, nutritional functional foods, and functional display foods.
  • the composition of the food and drink is not particularly limited, and examples thereof include various food materials, auxiliaries, stabilizers and the like in addition to the intestinal flora constituent ratio adjuster. Moreover, the said food-drinks can be manufactured by the formulation technique etc. which are used normally.
  • the target animal species of the food and drink is not particularly limited, and examples thereof include humans, non-human mammals such as monkeys, cows, pigs, dogs, and cats, birds such as chickens, and seafood.
  • mice 5-week-old male C57BL / 6J mice were fed with a normal diet (CE-2 solid sample, manufactured by CLEA Japan, Inc.) and water and reared for 2 days.
  • a normal diet (AIN-93M purified sample, manufactured by the National Nutrition Laboratory, USA) was given and the animals were raised for 5 days.
  • distilled water is added to 100 mg of the BP0899 strain to 10 mL, and a suspension is prepared by stirring with a vortex mixer. Further, 9 mL of distilled water is added to 1 mL of the suspension to make a total of 10 mL. A suspension was formed.
  • mice at 6 weeks of age were divided into a group (Example 1-1, 7 animals) in which the BP0899 strain intake was 10 mg / kg and a group (Example 1-2, 7 animals) in which 100 mg / kg was consumed. And divided. Then, the day after the grouping was set as the administration start date (day 1), and the BP0899 strain suspension was orally administered to each group daily from day 1 to day 14 using a sonde. In addition, instead of the BP0899 strain suspension, a control group in which the experiment was conducted in the same manner as in Example 1-1 and Example 1-2 except that distilled water was administered was compared with Comparative Example (Comparative Example 1, 7 animals). did. Then, feces analysis was performed on all three groups of Example 1-1, Example 1-2, and Comparative Example 1 as shown below.
  • Bacteroides (Bacteroides) genus component ratio Bacteroides (Bacteroides) genus component ratio (%) in 7 day, divided by Bacteroides in 3 day (Bacteroides) genus component ratio (%) The value was calculated. Then, the relative value (change rate) in Example 1-1 and Example 1-2 when the value in Comparative Example 1 was set to 1 was calculated. Bacteroides (Bacteroides) rate of change of the composition ratio of the enteric bacteria other than genus was also calculated in the same manner as Bacteroides (Bacteroides) genus.
  • 1 to 6 are graphs showing changes in the composition ratio of enteric bacteria in the mice of Example 1-1, Example 1-2, and Comparative Example 1 for each type of enteric bacteria.
  • Example 1-1 the rate of change was greater than 1, and the composition ratio of the genus Bacteroides was higher than in Comparative Example 1.
  • FIG. 2 in Example 1-1, the rate of change greatly exceeded 1, and the composition ratio of the genus Lactobacillus was extremely higher than that in Comparative Example 1.
  • Example 1-2 further exceeds the rate of change of the embodiment 1-1, an increase in composition ratio of Lactobacillus (Lactobacillus) genus in accordance with the dose of the BP0899 strain was confirmed.
  • FIG. 3 in Example 1-1, the rate of change was larger than 1, and the constituent ratio of the genus Prevotella was higher than that in Comparative Example 1.
  • Example 1-2 the rate of change of Example 1-1 was further exceeded, and an increase in the composition ratio of the genus Prevotella according to the dose of the BP0899 strain was confirmed.
  • the rate of change is greater than 1, the component ratio of Clostridium cluster XVIII (Clostridium claster XVIII), was higher than Comparative Example 1.
  • the rate of change was greater than 1, and the composition ratio of Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) was higher than in Comparative Example 1.
  • Example 1-1 and Example 1-2 the rate of change is greater than 1, the proportions of Clostridium cluster XI (Clostridium claster XI), was higher than Comparative Example 1.
  • the rate of change was greater than 1, indicating that in Comparative Example 1, the composition ratio of the subject intestinal bacteria increased from the third day on the seventh day.
  • the degree of increase was larger than that in Comparative Example 1, and the composition ratio of the target enteric bacteria in Comparative Example 1 was 3 days on the 7th day.
  • the degree of decrease in Example 1-1 and Example 1-2 was smaller than that in Comparative Example 1 (that is, the intestine of the subject in Example 1-1 and Example 1-2).
  • Example 1 a value obtained by dividing the composition ratio (%) of intestinal bacteria on days 8 to 15 by the composition ratio (%) of intestinal bacteria on day 3 was calculated and compared.
  • the value in Example 1 was set to 1
  • the relative value (change rate) in Example 1-1 and Example 1-2 was calculated.
  • FIG. 7 to 12 are graphs showing changes in the composition ratio of enteric bacteria in the mice of Example 1-1, Example 1-2, and Comparative Example 1 for each type of enteric bacteria.
  • Figure 11 the results of Clostridium subcluster XIVa (Clostridium subclaster XIVa)
  • FIG. 12 shows the results of Clostridium cluster XI (Clostridium claster XI). 7 to 12, the vertical axis represents the rate of change.
  • Example 1-1 and Example 1-2 the rate of change was larger than 1, and the composition ratio of the genus Bacteroides was higher than that in Comparative Example 1.
  • the rate of change was greater than 1, and the composition ratio of the genus Lactobacillus was higher than that in Comparative Example 1.
  • the rate of change was greater than 1, and the composition ratio of the genus Prevotella was higher than that in Comparative Example 1.
  • the rate of change is greater than 1, the component ratio of Clostridium cluster XVIII (Clostridium claster XVIII), was higher than Comparative Example 1.
  • FIG. 10 the rate of change is greater than 1, the component ratio of Clostridium cluster XVIII (Clostridium claster XVIII), was higher than Comparative Example 1.
  • Example 1-1 in Example 1-1 and Example 1-2, the rate of change greatly exceeded 1, and the composition ratio of Clostridium subcluster XIVa ( Clostridium subcluster XIVa ) was significantly higher than that in Comparative Example 1.
  • Figure 12 in Example 1-1, the rate of change greatly exceeded 1, the component ratio of Clostridium cluster XI (Clostridium claster XI), was extremely higher than Comparative Example 1.
  • Example 1-2 further exceeds the rate of change of the embodiment 1-1, an increase in component ratio of the BP0899 strain Clostridium cluster XI in accordance with the dose of (Clostridium Claster XI) was observed.
  • the intestinal flora constituent ratio is adjusted by at least one of Rhodobacter azotoforms BP0899 strain (Accession No. NITE BP-644) and its culture, For example, obesity, multiple sclerosis and the like can be improved. Since the intestinal flora constituent ratio adjusting agent of the present invention is highly safe, it can be administered over a long period of time. Therefore, according to the present invention, it is possible to provide a useful and highly safe intestinal flora constituent ratio regulator, pharmaceuticals and foods and drinks, and its application range is not limited and is wide.

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Abstract

La présente invention concerne un agent très sûr et nouveau pour réguler le rapport de composition de la flore bactérienne intestinale. L'agent de régulation du rapport de composition de la flore bactérienne intestinale selon la présente invention, qui régule le rapport de composition de la flore bactérienne intestinale, est caractérisé en ce qu'il comprend Rhodobacter azotoformans souche BP0899 (dépôt n° NITE BP-644) et/ou un produit de culture de celui-ci.
PCT/JP2017/016071 2016-04-26 2017-04-21 Agent pour réguler le rapport de composition de la flore bactérienne intestinale, médicament, aliment, boisson et procédé de régulation du rapport de composition de la flore bactérienne intestinale WO2017188157A1 (fr)

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EP17789440.9A EP3449932A4 (fr) 2016-04-26 2017-04-21 Agent pour réguler le rapport de composition de la flore bactérienne intestinale, médicament, aliment, boisson et procédé de régulation du rapport de composition de la flore bactérienne intestinale
US16/095,878 US20190125805A1 (en) 2016-04-26 2017-04-21 Agent for regulating composition ratio of the intestinal microbiota, drug, food, drink and method for regulating composition ratio of the intestinal microbiota
JP2018514568A JPWO2017188157A1 (ja) 2016-04-26 2017-04-21 腸内細菌叢構成比率調整剤、医薬品、飲食品及び腸内細菌叢構成比率の調整方法
KR1020187030171A KR20180137494A (ko) 2016-04-26 2017-04-21 장내 세균총 구성 비율 조정제, 의약품, 음식품 및 장내 세균총 구성 비율의 조정 방법
CN201780025931.9A CN109152802A (zh) 2016-04-26 2017-04-21 肠道菌群构成比率调节剂、药品、饮食品及肠道菌群构成比率的调节方法

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019181826A1 (fr) * 2018-03-23 2019-09-26 ティーエフケイ株式会社 Composé, agent de régulation des rapports de composition du microbiote intestinal, produit pharmaceutique, produit alimentaire/boisson, additif alimentaire, procédé de régulation des rapports de composition du microbiote intestinal, et procédé de production de composé

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CN110251582A (zh) * 2019-06-06 2019-09-20 嘉兴市爵拓科技有限公司 肠道菌群构成比率调节剂、药品、饮食品及肠道菌群构成比率的调节方法

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JP2010521136A (ja) * 2007-03-16 2010-06-24 キリンホールディングス株式会社 腸内細菌叢改善用組成物
WO2010123037A1 (fr) * 2009-04-22 2010-10-28 富士フイルム株式会社 Agent pour réguler la proportion de la composition de la flore bactérienne intestinale
WO2011102035A1 (fr) * 2010-02-16 2011-08-25 ティーエフケイ株式会社 Agent prophylactique/d'amélioration pour des maladies, agent d'amélioration de l'endurance et agent antifatigue, et agent pharmaceutique, aliment et boisson comprenant chacun l'un quelconque de ces agents

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JP2010521136A (ja) * 2007-03-16 2010-06-24 キリンホールディングス株式会社 腸内細菌叢改善用組成物
WO2010123037A1 (fr) * 2009-04-22 2010-10-28 富士フイルム株式会社 Agent pour réguler la proportion de la composition de la flore bactérienne intestinale
WO2011102035A1 (fr) * 2010-02-16 2011-08-25 ティーエフケイ株式会社 Agent prophylactique/d'amélioration pour des maladies, agent d'amélioration de l'endurance et agent antifatigue, et agent pharmaceutique, aliment et boisson comprenant chacun l'un quelconque de ces agents

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019181826A1 (fr) * 2018-03-23 2019-09-26 ティーエフケイ株式会社 Composé, agent de régulation des rapports de composition du microbiote intestinal, produit pharmaceutique, produit alimentaire/boisson, additif alimentaire, procédé de régulation des rapports de composition du microbiote intestinal, et procédé de production de composé

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US20190125805A1 (en) 2019-05-02
CN109152802A (zh) 2019-01-04
EP3449932A4 (fr) 2019-12-04
JPWO2017188157A1 (ja) 2019-02-28
KR20180137494A (ko) 2018-12-27

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